Sulfur-substituted mercaptodihydrosafroles



s PATENT oFF SULFUR-SUBSTITUTED MERGABTO- nmrnnossrnorns Edward A. .P'riu, lionke Nix; Thompsonlnstitute for v corporation of New York' assisnor t B y P ant Res a a No Drawing. Original application FebruaryS,

1946, Serial No; 646,492. Divided and this zipn ication June 15, 1.9 8, e ia 3 4 b aimsii-Wij.

- This invention has for its object the provision of certain new organic compounds. The com-l pounds of the invention compare favorably with or exceed the extracts of pyrethrin and rotenorie. bearing plants in toxicity to insects, are effective insecticides alone and also increase the effective.- ness of other insecticides. In admixtures with pyrethri-n, the compounds manifest pronounced synergistic effects. My Patent 2,493,927, issued January 1950, of which this application is a division, claims insecticidal compositions .comprising the compounds.

One of the advantageous features of the invention is that the compounds may be produced from readily available substances by a simple, practical, andeconomical manufacturing process. Another important feature of :the compounds of the inven tion is that they are readily soluble in the petroleum distillates commonly used as solvents for insecticidal sprays. w

The new compounds which I have conceived and synthesized areorganic sulfides belonging to the class of sulfur substituted mercaptodih-ydro, safroles in which :the substituted .mercapto sulfur atom is attached to :a carbon :atom of the side chain. 'These compounds are designated by :the general formula: r

where iris-an integer 2 or 3, mis an integer not greater than '3, and R is an univalent-radical of the group consisting of allcyl, aryl, alkaryl and ara-lkyl radicals, and nuclear -mono substituted aryl,-alkaryl and arallcyl-radi-cals in which the nuclear substituent is a member of the group consisting of halogen and alkoxy; and in-the above formula, therearenot-morethan 26 carbon atoms. The compounds of the invention can -bemade' by the peroxide catalyzed addition reaction of a mercaptan-of the formula HS(CiiH2n-'O-)'MLR, where mm, and Rare as previously defined, and a 3,4-methylenedioxyphenyl-propylene such as safrole and isosafrole. When safrole is used in=this reaction, the reaction is represented by the probable equation:

was isosafrol is use in hi e cti n. th reaction is represented b the p obable equat on 1 Frequentl -it is not necessary to specially pro.- v-ide an organic peroxide to catalyze the reaction because some-organic .peroxid-ic matter is already present as a resultof unavoided autoxidation of a-component of the reaction mixture. 7

The following general methods were used for th-eformation and-purification of the new compounds of this invention. r

0f the mercap-tans of the formula,

that were used as intermediates, some were ob.- tained from commercial sources and others were synthesized by the general laboratory method consisting of the reaction of a reactive chloroor bromocompound with thiourea and subsequent hydrolysis of the intermediary sulfur substituted thiourea salt to a mercaptan' In practice, however, themercaptans may-be produced by any suitable method. Asa special case, certain (of the-.mon omercaptans may be considerable .to be formed as intermediates in the reaction of a dimercapto compound, such as flfi'sdimercaptodiethylether, :with safroleor isosafrole. The in.- terrnediary monomercaptan, which also contains a zthio tether linkage, satisfies the description of the formula, HS,.(G1LHQne-Q:-)MR, and can in turn undergo further reaction with safrole .or

isosafrole. the formation .of the various insecticides, thijlWO reactants were mixedin the proportions indicatedv as. follows: 0:1 mole .of a .monomercaptan and 0.1.molelof safrole; .0.1.mole.of 31110110..- mercaptama-nd 0.1 .mole of ,isosafrole; 0.1 moleof 13,p .-.dimercaptodiethyL ether:.and.0.3 .mole, aliberal excess, .of safrole; and-0.21 .mole o flfi-dimercaptodiethyLether and.;0.3 lmole, a liberal excess, of isosafrole. :To :each mixture were added. a few dropsof .ascaridoleimorder .toinsure thepresence of 1a iperoxidic icatalyst. The reaction mixtures containing ethyl Imercaptan were-allowed to stand inpressure :bottles at room temperature for vtwo weekscin order :tobring about the .addition reaction. {Ihe addition reactions of n-butyl .mercaptan, p-tolyls-mercaptan, and benzyl mercaptan with isosafrole were similarly effected at room temperature,.;and it was also'rpossibleto. effect these additionreaetions more rapidly at @1001 V. a filotsallztherothfil':addltinnvreactions, :thereaction 3 mixtures contained in flasks provided with reflux condensers were warmed at about 100 C. on a steam table for about 48 hours. The addition. reaction of n-butyl mercaptan with safrole also was successfully effected at 100 C. by using a trace of benzoyl peroxide in place of ascaridole.

By using somewhat aged samples of safrole and isosafrole, the addition reactions of these with n-butyl mercaptan also were successfully effected at 100 C. Without the special addition of a peroxide.

At the termination of the reaction period, the reaction mixture was in each case mixed with petroleum ether or with ethyl ether when the compound was not sufficiently soluble in the former solvent, and the solution shaken with per cent aqueous potassium hydroxide to wash out any remaining mercaptan. The organic solvent was then evaporated. When possible, the product was fractionally distilled in vacuo. when so distilled, the boiling point ranges of the compound are indicated with the data in Table I and Table II. The other compounds,-which were non-distillable or difficult to distill, were purified by removalv of any steam distillable impurities as well as any unreacted safrole or isosafrole by steam distillation. The oily compound remaining in the distilling flask was then taken up in ethyl ether, the solution dried over anhydrous sodium sulfate, then filtered, and the solvent evaporated. The compounds which were purified by steam distillation were free of any unpleasant odor. The removal of any malodorous impurities by steam distillation is also applicable, to the compounds which were fractionally distilledin vacuo; however, those compounds made with butyl or lower molecular weight mercaptans also may pass into the steam distillate to an appreciable extent if, the steam distillation process is prolonged. Steam distillation may be employed in lieu of fractional distillation in vacuo, .or subsequent thereto, to remove the last trace of any malodorous impurity. Of. the compounds prepared, all were viscous oily liquids at room temperature. All of the compounds with the exception of those containing a tetrahydrofurane residue or a benzene nucleus in the substituent were very soluble in Deo-Base, a purified petroleum distillate.

Various adaptations of the process of making the compounds may be used. After termination of the reaction period, the crude product may be used directly for insecticidal purposes, or any unreaoted mercaptan only may be removed by a process such as Washing with an aqueous solution of an alkali. Any safrole or isosafrole remaining in the product ordinarily would not be objectionable. The reactants may be used in any proportions except when a dimercapto compound is used, in which case the molar concentration of a dimercapto compound should not be more than onehalf the molar concentration of the other reactant. Any excess mercaptan may be recovered by extraction or distillation and any excess safrole or isosafrole either may be recovered by direct distillationor steam distillation, or it may be left in the product. In general, safrole, isosafrole, a mixture of safrole and isosafrole or an essential oil containing a substantial amount of safrole, isosafrole or both may be used in the reaction with a mercaptan or a mixture of mercaptans, and the crude product may be used directly, or it may be subjected to any of previously outlined methods for partial or' complete purification. Any of a great variety of organic peroxidlc substances'may be used as catalyst, or peroxidic substancesnaturally present-as a result of autoxidation may serve the purpose. Any reaction temperature from room temperature up to a temsidered usable.

In addition to the compounds that are presented herein as specific examples, the compounds ofthe invention maybe any other compound of the class which bears a suitable substituent radical containing not more than sixteen carbon The substituent radical may be any one atoms. of the following radicals: an alkyl, an alkenyl, an aralkyl, a nuclear halogenated ,aralkyl, a nuclear alkyl substituted aralkyl, an alkyl substituted aryl, a methylenedioxyphenylalkyl, a cycloalkyl-alkyl, and. a radical characterized as being any of the above-listed radicals in which the contingent relation of the carbon atoms is interrupted by one or more oxygen atoms in ether structure or by one or more sulfur atoms in thio ether structure, or by both; also airadical containing as substituent to an alkyl or to an oxygen interrupted alkyl radical, a cyclic ether structure, such as a tetrahydrofurane residue, a tetrahydropyran residue, a dioxane residue, or the like; also a cycloalkyl, an arylcycloalkyl, an aryl, and a nuclear halogenated aryl.

Spray solutions containing the compounds of this invention were tested against houseflies by the Large Group Peet-Grady Method (Blue Book pp. 177181,, MacNair-Dorland Co., New York, 1939). Control tests with the Official Test Insecticide (OTI) (Soap and Sanitary Chemicals 21 (6) 137, 141, June, 1945), which contains approximately 0.1 g. of pyrethrins per 100 ml., also were carried out on each batch of flies used. The compounds, except those containing a tetrahydrofurane residue or abenzene nucleus in the substituent radical, were dissolved in Deo-Base, a purified petroleum distillate. The compounds containing a tetrahydrofurane residue or a benzene nucleus in the substituent radical were dissolved in a mixture of Deo-Base and not more than 5 per cent acetone. Solutions of some of the compounds without added pyrethrins were tested. One or more solutions of each of the compounds in admixture'with small amounts of pyrethrins were tested, the amount of admixed pyrethrins being 0.025 or 0.05 g. per 100 ml. Tests onssolution containing pyrethrins alone in the amountof 0.025 g. per 100 ml. showed an average l'0- minute knockdown of 84 per cent and,,after adjusting the 24-hour kills to an OTI kill of 50 per cent, an average 24-hour adjusted kill of 21 percent. 7 Tests on solutions containing pyrethrins. alone ;,i n the amount of0.5 g. per 100 ml. showed an average 10-minute knockdown of 93 percent, and after adjusting the 24-hour kills to an OTI kill of 5 0 per cent, an average adjusted kill of 32 per cent.

TableI gives the results of the tests with solutions containing members of the series of compounds made from safrole and mercaptans, and Table II gives the results ofthe tests with solutions containing members of the series of compounds made from isosafrole and mercaptans.

The compounds tested without admixed pythey exhibit synergistic action, the pyrethrins also contributing to a rapid knockdown.

airlinesethereal oxygen in the substituent radical regula-rly' showed greater insecticidal activity toward houseflies than did the related compounds which do not contain ethereal oxygen in the substituent.

This was most evident when comparison is made of the results obtained with solutions containing 0.025 g. admixed pyrethrins per 100 inl.

A compound made from isosafrole and; a mercaptan containing ethereal oxygen frequently showed a greater insecticidal activity toward houseflies than did a compound made from safrole and the same mercaptan.

Each of the compounds when tested in admixture with a small amount of pyrethrins contributed to a higher percentage -minute knockdown than could be attributed to the pyrethrins alone. A practical application of this is the use of a compound of the class in admixture with 2,2-bis-p chlorophenyl 1, 1, 1 trichloroethane (DDT) and a minimum amount of pyrethrins. DDT is an excellent insect killer, but it produces a very low knockdown and for this reason pyrethrins are often admixed with it to provide a rapid knockdown. It is shown by the data for compound No. 3 of Table I and compound No. 16 of Table II that by halving that amount of pyrethrins, which when used in admixture with DDT produced an inadequate 10-minute knockdown, and adding a compound of this invention, a more satisfactory knockdown was obtained as well as an increased kill.

The fact that the marked insecticidal properties of the compounds of this invention were not pre-existent as attributes of any of the substances from which the compounds were made by a process of chemical combination is shown by the following results. A spray solution containing 3 g. of safrole and 0.025 g. of pyrethrins per 100 ml. and a spray solution containing 3 g. of isosafrole and 0.025 g. of pyrethrins per 100 ml.

"which were tested against houseflies were also ficantly greater kills than were given by the small amounts of pyrethrins alone.

Representative members of the compounds tested against certain agricultural insects. For these tests a weighed amount of a; compound dissolved in 10 ml. of acetone was mixed with 90 ml;

of a 0.1 per cent solution of sodium lauryl sulfate, the resulting emulsion sprayed on insect infested leaves and, after holding the sprayed insect infested leaves in Petri dishes for 20 hours, the results were determined,

When the insecticides were tested against Aphis on nasturtium leaves, a percentage kill of over 70 percent was obtained with a 0.1 per cent emulsion of each of the following compounds: Numbers 3, 9 and 10 of the compounds listed in Table I, and numbers 16, 24 and 25 of the compouiids listed in Table 11.

When the insecticides were tested against pea aphids on horse bean leaves, a percentage kill of each gave a knockdown and a kill which-were not I significantly different from the knockdown and the kill given by 0.025 g'. pyrethrins alone per 100 ml. Also several of the mercaptans of the types used in the preparation of the compounds, when similarly tested in the form of solutions with admixed small amounts of pyrethrins, caused no.

significantly greater knockdowns and no signiover 78 per cent was obtained with a 0.1 per cent emulsion of each of the following compounds: Numbers 3, 9 and 10of the compounds listed in Table I, and numbers 16, 24 and 25 of the compounds listed in Table II.

When the insecticidies were tested against onion thrips on onion leaves, a percentage kill of over 80 per cent was obtained with a 0.1 per cent emulsion of each of the following: Numbers 16 and} 25 of the compounds listed in Table III.

When the insecticides were tested against a thrips species on chicory leaves, a percentage kill of dver 8'7 per cent was obtained by the use of a 0.1 per cent emulsion of each of the following compounds: Numbers 3, 9 and 10 of the compounds listed in Table I and numbers 16, 24 and 25 of the compounds listed in Table II.

When similar tests were performed on Mexican bean beetle larvae on bush bean leaves with the use of 0.2 per cent emulsion of each of the following compounds, number 7 of the compounds listed in Table I, and numbers 16, 24 and 25 of the compounds listed in Table II, a few of the larvae were killed in each instance, but it was significant that no feeding occurred during the 48 hour period of the test. This shows that the compoundsihad a repellant action against this insect. 5

Tdble I I Results of the Peet- Grady tests on houseflies with solutions containing compounds of the probable formula:

each of said compounds being the peroxide catalyzed addition reaction product of equlmolar portions of safrole and a mercaptan of'the' iormulai HS(C,.H1, ,-O-'-) m'R Boiling I v l o lfl-Minute 24-Hour 24-Hourcrease p gd o.H2.o-),,.R 3 53 pound, gffggg f lmockdown, kill, OIIkill, lff gfii fl I ...P ..".."??i if"??? it??? 2959 1 (CH2)BO-C2H5 E Z-Etgyoxyethyl 1.2 00.2.5. 95 87 55 +32: 0 96 79 I 57 1 +22 2 (CH 2 n-Butoxyeth 1.0 O 84 80 63 +1T o .2 .05 9s 81 50 +31;

uso mwon 10-Min- 1 Bollmg Increase Com- Oomute 24-Hour 24-Hour pound (OnH1n )mR gag pound, g fgg g k-nock- 1 kilLPer OT-I ki11,, gggfgfi Y 1 K 7 No. v OClmm. g./10O n11. P221621: Cent Per Cent Per Cent 14 -(OHE)1OCH5 2-Ethoxyethyl 164-167/1 1.0 0. .83. 76 55; +21 -.do .4 .025 99 87 57 15 0H=' =0-(0H)3cH3 1 1 2-I1-Butoxyethyl .1e9-172/1 1.0 78 63; +15 fin .4 so 62; +24 do .2 90 51 5 +39 16 (CH2)2-0-(CHz)z'O(CHz)aCH; v t

2-(2-n-Butoxyethyoxy)ethy1 194-197/1 .4 71. 55 +16 do .4 I '90 55 2 76 55 +21 1 69 52 +17 15 42 +2 "0 69 40 +29 fin 15 87 40 +47 11 2)7-- z)2 2)sC s 2-(2-11-Hexy1oXyeth :a'th -I 1.0 82 55 +27 do flffnn j .2 69 51 +13 2-[2-(2-n-Butoxyethoxy)ethoxy]ethyl. 1. 0 0 94(97) .96 62 +34 o .2 .025 9s 78 62 +16 19 CH2''-CH2 l t I (-om a-o-omon--o-cm &

3-Tettahydrofurfur5' 1ox m f 1.0 92 91 as +25 .."do .4 99 '98 '62 +36 'dn w 9 1541 51 +13 cH=cm :20

( n)2O'(OH2)2O'CHa( JH-O- OHa v 1 2-(Z-Tetrahydxofuriuryloxyethoxwethyl 1 0 0 97 '97 55 +42 do 2 .025 97 64 2 Phenoxyethyl 1. 0 0 80 77 66 +11 .--.do .2 025 94 71 48 +28 22 cHm0-o1 2-(p-Ohlorophenoxy)ethyl 1. 0 0 73 72 +17 .do .2 .025 94 68 45 +23 1 2a z):OC

2-(2-Phenoxyethoxy)ethyl 1. 0 94 94 65 +29 do 4 96 0 50 +4 do .2 97 73 45 +28 25 -(OHz)z0CHz Z-Benzoxyethyl 1. 0 90 (93) 91 65 +26 fln ,2 98 45 +30 1 98 60 41 +19 Table II Results of thoPeot-Grady tests onhouseflies with solutions containing compounds of the probable formula:

each of said compounds being the peroxide catalyzed addition reaction product of equimolar portions of isosafnole and a mercaptan of the formula formula:

formula: r

TabZaII- -Continued i v IO-Min- Boiling Increase 5.3521 cnnn-o-mn g;j; "p3f1d, 235535 33kif ii fiiii, 53 No. VVOO'/mm g./100 m1. Piggtlcflelglt Cent Per Cent Per Cent 26 -(oH2 3-0C 0 o113 3-(p-Methoxyphenoxy)propy1 .L 1.0 0 88(92) 88 62 +26 .do .4 .025 97 81 60 +21 2 on2 r-o(0H2)i-0 v 0-011 2-[2-(n-Methoxyphenoxy)ethoxy]ethyl .4 .025 99 94 53 +41 (cH2 2-o cm 2 O S OH([3H 28 OH: 1.0 o 65(66) .65 .46 +19 O i do .2 .025 95 70 46 +24 (this compound being made from two moles of ISO- salflroge and one mole of Bfi-dimercaptodiethyl et er The figures indicated in parentheses are the percentages of the knockdown based upon the number of flies that were down at the end of the process of picking up the paralyzed flies. This was about 15 minutes after application of the spray.

I claim:

2. An organic compound represented by the 40V 3. An organic compound represented by the atoms 'No references cited.

4. An organic compound represented by the where n is an integer 2 or 3, m'is an integer not greater than 3, and R is an univalent radical of the group consisting of alkyl, aryl, al-karyl and aralkyl radicals, and nuclear mono substituted aryl, alkaryl and aralk'yl radicals in which the nuclear substituent is a member of the group consisting of halogen and alkoxy; and in the above formula, there are not more than 26 carbon EDWARD 'A. PRILL. 

4. AN ORGANIC COMPOUND REPRESENTED BY THE FORMULA 